Association of cardiac events with coronary artery disease detected by 64-slice or greater coronary CT angiography: a systematic review and meta-analysis.

BACKGROUND: The value of ≥64-slice coronary CT angiography (CCTA) to determine odds of cardiac death or non-fatal myocardial infarction (MI) needs further clarification. METHODS: We performed a systematic review and meta-analysis using publications reporting events/severity of coronary artery disease (CAD) in patients with suspected CAD undergoing CCTA. Patients were divided into: no CAD, non-obstructive CAD (maximal stenosis <50%), and obstructive CAD (≥50% stenosis). Odds ratios with 95% confidence intervals were calculated using a fixed or random effects model. Heterogeneity was assessed using the I(2) index. RESULTS: We included thirty-two studies comprising 41,960 patients with 363 all-cause deaths (15.0%), 114 cardiac deaths (4.7%), 342 MI (14.2%), 69 unstable angina (2.8%), and 1527 late revascularizations (63.2%) over 1.96 (SD 0.77) years of follow-up. Cardiac death or MI occurred in 0.04% without, 1.29% with non-obstructive, and 6.53% with obstructive CAD. OR for cardiac death or MI was: 14.92 (95% CI, 6.78 to 32.85) for obstructive CAD, 6.41 (95% CI, 2.44 to 16.84) for non-obstructive CAD versus no CAD, and 3.19 (95% CI, 2.29 to 4.45) for non-obstructive versus obstructive CAD and 6.56 (95% CI, 3.07 to 14.02) for no versus any CAD. Similar trends were noted for all-cause mortality and composite major adverse cardiovascular events. CONCLUSIONS: Increasing CAD severity detected by CCTA is associated with cardiac death or MI, all-cause mortality, and composite major adverse cardiovascular events. Absence of CAD is associated with very low odds of major adverse events, but non-obstructive disease significantly increases odds of cardiac adverse events in this follow-up period.

Photochemical transformation and phototoxicity of 1-aminopyrene.

1-Aminopyrene (1-AP) is an environmental mutagen and a metabolite of 1-nitropyrene (1-NO2P). On light irradiation, 1-AP transforms into oxidation products with a half-life of 7.1 min in 10% methanolic buffer. The presence of DNA or free-radical/ singlet oxygen scavengers 1,4-dithiothreitol, histidine, or NaN3 slows down 1-AP photochemical reaction. The photoproducts identified include 1-hydroxyaminopyrene, 1-nitrosopyrene, 1-NO2P, 1-amino-x-hydroxypyrene, and three covalent dimers. Since it is known that 1-NO2P and 1-nitrosopyrene are genotoxic and 1-hydroxyaminopyrnene can react with DNA to form covalent adducts, we used the Mutatox test to assess the toxicity of 1-AP and its photoproducts. It was found that the lowest-observed-effect concentrations for 1-AP, 1-AP photoproducts, and 1-NO2P are 1.25 microM, 10 microM, and NA (no mutagenic response was seen at this concentration range) in direct medium (no S-9) and NA, 5 microM, and 0.625 microM in S-9 medium, respectively. Therefore, 1-AP photoproducts are more genotoxic than 1-AP itself in the S-9 medium and more mutagenic than 1-NO2P in the direct medium. Thus, 1-NO2P alone cannot account for all the mutagenicity of the photoproducts. Irradiation of 1-AP together with DNA leads to covalent DNA adduct formation possibly via the 1-hydroxyaminopyrene intermediate. In this study, ultraviolet-A (UVA) was used at approximately the same magnitude as the outdoor UVA irradiance. Considering the half-life of 1-AP in the test solutions in this study, the aquatic biota (including humans) near the surface layer of a static water body are most likely subjected to the photoinduced toxicity of the study compound. The biota at the lower depths will also be affected if turbulence becomes a significant factor in enhancing the exposure risk for aquatic organisms.